Background Thyroid fine‐needle aspiration (FNA) plays a key role in triaging thyroid nodules. Yet many cases are assigned to indeterminate categories. The new category “noninvasive follicular thyroid neoplasm with papillary‐like features” (NIFTP) complicates thyroid cytology. Digital image‐derived nuclear measurements might objectively distinguish papillary thyroid carcinoma (PTC) from benign nodules and NIFTP. Methods All thyroid FNAs from 2012 to 2016 of atypia of undetermined significance (A; n = 8) and suspicious for malignancy (S; n = 2) with sufficient cellularity and surgical follow‐up, all FNAs preceding NIFTP (n = 6), and a random sample of PTC (n = 9) and benign (n = 10) cytology were studied. A modified Giemsa‐stained slide from each case was scanned using the Aperio imaging system, and long (dl) and short (ds)‐axis diameters were measured for 125 nuclei per case. Nuclear area and elongation were calculated. Results Nuclear area was larger in PTC (mean, 77.2 μm2 [range, 70.6‐86.0 μm2]) than benign (mean, 43.3 μm2 [range 38.2‐52.2 μm2]) (P < .001). Nuclear areas from indeterminate FNAs segregated according to final histology (A/S PTC mean 72.7 μm2, A/S benign mean 53.7 μm2; P = 0.004), and were not significantly different from definitive FNAs of the same diagnosis. NIFTP nuclear area was smaller than PTC (mean, 54.8 μm2 [range, 46.7‐66.1 μm2]; P < .001). Nuclear elongation showed similar results, but with greater group overlap. Conclusion Nuclear area and elongation can be calculated using a commercial digital imager; both correlate with the final surgical pathology diagnosis of PTC versus benign, including NIFTP. Area provides greater resolution than elongation. This technique could be used to resolve indeterminate cytology in which PTC is considered.

BackgroundPreterm infants (PTI) in the NICU are often placed in incubators that may increase their exposure to volatile organic chemicals (VOCs). To determine whether PTI in incubators have higher urinary concentrations of VOC metabolites compared with infants in cribs.MethodsUrine from 40 PTI in incubators and 40 infants in cribs was collected and analyzed for 28 urinary VOC biomarkers. Differences in metabolite concentrations between the two groups were compared.ResultsTwenty two of the VOC metabolites were detected in at least one urine sample. All urine samples tested had measurable levels of six VOC metabolites. Biomarkers for acrolein, acrylonitrile, carbon disulfide, cyanide, N-dimethylformamide, ethylbenzene, ethylene oxide, propylene oxide, styrene, toluene/benzyl alcohol, vinyl chloride, and xylene were higher in the incubator group. The geometric means of five VOC metabolites were 2-fold higher than those reported for NHANES children 6-11 years of age in one or both of the groups with benzyl mercapturic acid being 7-fold and 12-fold greater than NHANES in the crib and incubator group, respectively.ConclusionAll infants were exposed to VOCs. PTI in incubators have a different VOC exposure profile compared with infants in cribs. The health implications associated with these exposures require further study.

Although KMT2D, also known as MLL2, is known to play an essential role in development, differentiation, and tumor suppression, its role in pancreatic cancer development is not well understood. Here, we discovered a novel signaling axis mediated by KMT2D, which links TGF-β to the activin A pathway. We found that TGF-β upregulates a microRNA, miR-147b, which in turn leads to posttranscriptional silencing of KMT2D. Loss of KMT2D induces the expression and secretion of activin A, which activates a non-canonical p38 MAPK-mediated pathway to modulate cancer cell plasticity, promote a mesenchymal phenotype, and enhance tumor invasion and metastasis in mice. We observed a decreased KMT2D expression in human primary and metastatic pancreatic cancer. Furthermore, inhibition or knockdown of activin A reversed the pro-tumoral role of KMT2D. These findings reveal a tumor-suppressive role of KMT2D and identify miR-147b and activin A as novel therapeutic targets in pancreatic cancer.

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